6474-90-4Relevant articles and documents
A Radical Cascade Enabling Collective Syntheses of Natural Products
Wang, Xiaobei,Xia, Dongliang,Qin, Wenfang,Zhou, Ruijie,Zhou, Xiaohan,Zhou, Qilong,Liu, Wentao,Dai, Xiang,Wang, Huijing,Wang, Shuqing,Tan, Ling,Zhang, Dan,Song, Hao,Liu, Xiao-Yu,Qin, Yong
, p. 803 - 816 (2017/06/13)
Natural products have long been important inspirations for the development of chemical methodologies, theories, and technologies, and ultimately, discoveries of new drugs and materials. Chemical syntheses have traditionally yielded individual or small groups of natural products; however, methodology development allowing the synthesis of a large collection of natural products remains scarce. Here, we report an efficient photocatalytic radical cascade method that enables access to libraries of chiral and multiple-ring-fused tetrahydrocarbolinones. The radical cascade can controllably introduce complexity and functionality into products with excellent chemo-, regio-, and diastereoselectivity. The power of this distinct method has been demonstrated by the efficient syntheses of 33 monoterpenoid indole alkaloids belonging to four families.
ENANTIOSELECTIVE SYNTHESES OF HETEROYOHIMBINE NATURAL PRODUCT INTERMEDIATES
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Paragraph 00070; 00071, (2016/11/21)
Enantioselective syntheses of cis- and trans-bicyclic dihydropyran compounds, and other intermediates, en route to heteroyohimbine alkaloids.
Enantioselective syntheses of heteroyohimbine natural products: A unified approach through cooperative catalysis
Younai, Ashkaan,Zeng, Bi-Shun,Meltzer, Herbert Y.,Scheidt, Karl A.
, p. 6900 - 6904 (2015/06/08)
Alstonine and serpentine are pentacyclic indoloquinolizidine alkaloids (referred to as "anhydronium bases") containing three contiguous stereocenters. Each possesses interesting biological activity, with alstonine being the major component of a plant-based remedy to treat psychosis and other nervous system disorders. This work describes the enantioselective total syntheses of these natural products with a cooperative hydrogen bonding/enamine-catalyzed Michael addition as the key step. The enantioselective total syntheses of the natural products alstonine and serpentine are presented. They proceed through a sequence with a cooperative hydrogen bonding/enamine-catalyzed Michael addition as the key step.
A facile chemoenzymatic approach: One-step syntheses of monoterpenoid indole alkaloids
Zou, Hong-Bin,Zhu, Hua-Jian,Zhang, Liang,Yang, Liu-Qing,Yu, Yong-Ping,Stoeckigt, Joachim
experimental part, p. 2400 - 2404 (2011/08/04)
Facile chemoenzymatic syntheses of cytotoxic monoterpenoid indole alkaloids with novel skeletons and multiple chiral centers are described. Synthesis of these alkaloids was achieved by a simple one-step reaction using strictosidine and 12-aza-strictosidine as the key intermediates. Strictosidines were prepared by coupling of secologanin with tryptamine and 7-aza-tryptamine, respectively, using the immobilized recombinant Rauvolfia strictosidine synthase. A detailed stereochemical analysis is presented herein. The results provide an opportunity for a chemoenzymatic approach that leads to an increased diversification of complex alkaloids with improved structures and activities.
Construction and expression of a dual vector for chemo-enzymatic synthesis of plant indole alkaloids in Escherichia coli
Stoeckigt, Joachim,Hammes, Bodo,Ruppert, Martin
scheme or table, p. 759 - 766 (2010/09/07)
A dual vector (pQE-70-STR1-SG) containing coding regions of strictosidine synthase (STR1, EC 4.3.3.2) and strictosidine glucosidase (SG, EC 3.2.1.105) from the Indian medicinal plant Rauvolfia serpentina was constructed. Functional expression of the vector in Escherichia coli cells (M15 strain) was proven by isolation of prepurified enzyme extracts, which show both STR1 and SG activities. Incubation of the enzyme in the presence of tryptamine and secologanin delivered the indole alkaloid cathenamine, demonstrating functional co-expression of both STR1- and SG-cDNAs. Cathenamine reduction by sodium borohydride leading to tetrahydroalstonine revealed the chemo-enzymatic indole alkaloid synthesis.
Unified strategy for synthesis of indole and 2-oxindole alkaloids
Martin, Stephen F.,Benage, Brigitte,Geraci, Leo S.,Hunter, James E.,Mortimore, Michael
, p. 6161 - 6171 (2007/10/02)
A concise and general entry to representative indole alkaloids of the yohimboid, heteroyohimboid, corynantheoid, and 2-oxindole classes has been developed exploiting a strategy that features intramolecular Diels-Alder reactions for the facile construction of the D/E ring subunits of the target alkaloids. The efficacy of the approach is first illustrated by a two-step total synthesis of the yohimboid alkaloid oxogambirtannine (2) from 22. Thus, the Diels-Alder substrate 25, which was prepared by nucleophilic addition of vinyl ketene acetal 24 to the intermediate N-acyliminium salt formed in situ upon reaction of 22 with 23, was heated in the presence of benzoquinone to give a mixture of diastereoisomeric cycloadducts 26 and 27; these adducts underwent spontaneous oxidation to furnish 2. In another application of the strategy, the [4+2] heterocyclization of 34a, which was formed upon nucleophilic addition of 1-[(trimethylsilyl)oxy]butadiene to the N-acyliminium salt generated in situ upon treatment of 22 with crotonyl chloride, afforded a mixture (ca. 9:1) of cycloadducts 35a and 36a. The major adduct 35a was converted to 42a using a general procedure for effecting β-carbomethoxylation of enol ethers to give vinylogous carbonates. Subsequent reduction of 42a to the heteroyohimboid alkaloids (±)-tetrahydroalstonine (3) and (±)-cathenamine (4) was achieved by selective delivery of 2 or 1 equiv of hydride, respectively. When 42a was treated with sodium amide, stereoselective β-elimination ensued to give 49, which was converted by chemoselective hydride reduction into the corynantheoid alkaloid (±)-geissoschizine (5). Facile access to alkaloids of the 2-oxindole family was realized by using a new protocol for achieving stereoselective, oxidative rearrangements of β-carboline Nb lactams into 3,3-disubstituted 2-oxindoles. Thus, exposure of 42a to tert-butyl hypochlorite followed by acid and silver ion induced rearrangement of the intermediate 3-chloroindolenine gave 50, with only traces of the C(7) epimer being detected. Hydride reduction of 50 gave (±)-isopteropodine (6), acid-catalyzed isomerization of which furnished an equilibrium mixture (1:3) of 6 and (±)-pteropodine (51). The stereochemical course of the intramolecular hetero-Diels-Alder reaction of 34a to give 35a and 36a as the only isolable cycloadducts was examined by computational analysis. The geometry of the six-atom transition state was established by semiempirical methods by using the standard closed-shell, restricted Hartree-Fock (RHF) version of the AM1 method. With use of this constrained geometry for the six-membered pericyclic array, the overall conformational energies for the four possible transition states 52-55 were minimized by MM2 calculations (MacroModel). The calculated relative energies of these transition states were in the order 52 53 54 55. Since the cyclization of 34a produced only 35a and 36a in an approximately 9:1 ratio via the respective transition states 52 and 53, these calculations correlated qualitatively with the experimental results.
Stereo-controlled Synthesis of (-)-Ajmalicine and (-)-Tetrahydroalstotine
Takano, Seiichi,Satoh, Shigeki,Ogasawara, Kunio
, p. 59 - 60 (2007/10/02)
Stereo-controlled synthesis of the heteroyohimbine alkaloids, (-)-ajmalicine and (-)-tetrahydroalstotine, has been developed starting from diethyl L-tartrate by employing the intramolecular hetero-Diels-Alder reaction as the key step.
Chloroformate Ester-induced Reductive 1,2-Bond Cleavage of 1,2,3,4-Tetrahydro-β-carboline Derivatives: Stereochemistry and Application in Sequence with an Oxidative Bond Regeneration Reaction to the Synthesis of Indole Alkaloids
Calverley, Martin J.
, p. 1848 - 1890 (2007/10/02)
Treatment with a chloroformate ester at -70 deg C and subsequent reaction with NaBH3CN converts 1,2,5,6,11,11b-hexahydro-3H-indoloindolizine and derivatives of 1,2,3,4,6,7,12,12b-octahydroindoloquinolizine cleanly into corresponding C/D ring-cleaved urethane derivatives.Oxidation of the products with 1-chlorobenzotriazole in dichlormethane or in methanol as a participating solvent refunctionalises the centre, reduced during the cleavage reaction and permits a formal reversal of that reaction.The overall result in the case of the quinolizidine derivatives is partial epimerisation at C-12b, a process which is exemplified in the syntheses of methyl(+/-)-geissochizoate and akuammigine from their respective epimers.The sequence finds its application par excellence in the synthesis of the pentacyclic mavacurine skeleton, in wich chirality at C-12b is re-established dependently during ring regeneration after oxidation in the presence of Et3N.The same reaction provides test implications for an investigation of the stereochemistry of the reductive cleavage reaction, during wich the incorporation of deuterium (from NaBD3CN) is shown by chemical correlation to proceed with stereospecific inversion of configuration.
